PUBLICATION

Genome-wide association and functional follow-up reveals new Loci for kidney function

Authors
Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, C.A., Fuchsberger, C., Olden, M., Chen, M.H., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, M.C., O'Seaghdha, C.M., Glazer, N., Isaacs, A., Liu, C.T., Smith, A.V., O'Connell, J.R., Struchalin, M., Tanaka, T., Li, G., Johnson, A.D., Gierman, H.J., Feitosa, M., Hwang, S.J., Atkinson, E.J., Lohman, K., Cornelis, M.C., Johansson, A., Tönjes, A., Dehghan, A., Chouraki, V., Holliday, E.G., Sorice, R., Kutalik, Z., Lehtimäki, T., Esko, T., Deshmukh, H., Ulivi, S., Chu, A.Y., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, T.B., Launer, L.J., Aspelund, T., Eiriksdottir, G., Mitchell, B.D., Boerwinkle, E., Schmidt, H., Cavalieri, M., Rao, M., Hu, F.B., Demirkan, A., Oostra, B.A., de Andrade, M., Turner, S.T., Ding, J., Andrews, J.S., Freedman, B.I., Koenig, W., Illig, T., Döring, A., Wichmann, H.E., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, H.E., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Nöthlings, U., Jacobs, G., Biffar, R., Endlich, K., Ernst, F., Homuth, G., Kroemer, H.K., Nauck, M., Stracke, S., Völker, U., Völzke, H., Kovacs, P., Stumvoll, M., Mägi, R., Hofman, A., Uitterlinden, A.G., Rivadeneira, F., Aulchenko, Y.S., Polasek, O., Hastie, N., Vitart, V., Helmer, C., Wang, J.J., Ruggiero, D., Bergmann, S., Kähönen, M., Viikari, J., Nikopensius, T., Province, M., Ketkar, S., Colhoun, H., Doney, A., Robino, A., Giulianini, F., Krämer, B.K., Portas, L., Ford, I., Buckley, B.M., Adam, M., Thun, G.A., Paulweber, B., Haun, M., Sala, C., Metzger, M., Mitchell, P., Ciullo, M., Kim, S.K., Vollenweider, P., Raitakari, O., Metspalu, A., Palmer, C., Gasparini, P., Pirastu, M., Jukema, J.W., Probst-Hensch, N.M., Kronenberg, F., Toniolo, D., Gudnason, V., Shuldiner, A.R., Coresh, J., Schmidt, R., Ferrucci, L., Siscovick, D.S., van Duijn, C.M., Borecki, I., Kardia, S.L., Liu, Y., Curhan, G.C., Rudan, I., Gyllensten, U., Wilson, J.F., Franke, A., Pramstaller, P.P., Rettig, R., Prokopenko, I., Witteman, J.C., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Heid, I.M., Goessling, W., Chasman, D.I., Kao, W.H., and Fox, C.S.
ID
ZDB-PUB-120409-12
Date
2012
Source
PLoS Genetics   8(3): e1002584 (Journal)
Registered Authors
Garnaas, Maija, Goessling, Wolfram, Hastie, Nicholas D., Imboden, Medea
Keywords
Embryos, Genetic loci, Chronic kidney disease, Kidneys, Genome-wide association studies, Meta-analysis, Diabetes mellitus, Edema
MeSH Terms
  • African Americans/genetics
  • Aged
  • Animals
  • Caspase 9/genetics
  • Cyclin-Dependent Kinases/genetics
  • DEAD-box RNA Helicases/genetics
  • DNA Helicases/genetics
  • Female
  • Follow-Up Studies
  • Gene Knockdown Techniques
  • Genome-Wide Association Study*
  • Glomerular Filtration Rate/genetics*
  • Humans
  • Kidney/physiopathology*
  • Kidney Failure, Chronic/genetics*
  • Kidney Failure, Chronic/pathology
  • Male
  • Middle Aged
  • Phosphoric Diester Hydrolases/genetics
  • Whites/genetics
  • Zebrafish/genetics*
PubMed
22479191 Full text @ PLoS Genet.
Abstract

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping